Our broad, long-term objective is to develop knowledge needed for the control and treatment of tuberculosis. Specific research aims are as follows: 1) To determine the incidence of Mycobacterium tuberculosis (M. tb.) infection in HIV-infected and uninfected injecting drug users (IDUs), sexual partners of IDUs, and children in contact with TB-infected adults; 2) To identify risk factors for development of M. tb. infection; 3) To describe the natural history of M. tb. disease in children and adults; 4) To investigate the epidemiology of specific strains of M. tb. identified through restriction-fragment-length polymorphisms (RFLP) patterns of clinical isolates; 5) To evaluate the effect of M. tb. coinfection on the rate of progression of HIV disease; and 6) To investigate factors influencing compliance with tuberculosis prophylaxis and therapy. New York City is faced with a dramatic resurgence of tuberculosis, including an increase in drug-resistant strains. The proposed research will provide urgently needed information regarding incidence, risk factors, natural history, molecular epidemiology, treatment, and prevention of tuberculosis in an especially vulnerable multi-ethnic inner-city population with a high HIV seropositivity rate. The project will study the above-list critical issues regarding TB prospectively and retrospectively in three groups of patients: (1) intravenous drug users and their sexual contacts in an already-recruited cohort; (2) children who receive their primary care at Bellevue Hospital Medical Center; and (3) Bellevue Hospital Center inpatients with TB and outpatients undergoing prophylactic treatment. In addition to environmental risk factors (e.g., hopelessness, cohabitation with tuberculosis patients and injected drug use), we will investigate host factors, including: (a) HIV infection; (b) immune status among HIV- seropositive persons, as indicated by quantitative p24 antibodies; CD4, CD8, and gammadelta T cell counts; and (c) race, age, and nutritional status Incidence and risk-factors in the cohort will be assessed by interview, blood draw, PPD screening, medical record review, and anergy panel. Natural history and impact on HIV disease in adult and pediatric populations will be assessed by interviews, clinical screening and laboratory measures. Drug sensitivity testing and RFLP typing of specimens from the two populations will be conducted, respectively, at the Bellevue Mycobacteriology Lab and the Public Health Research Institute. Factors affecting treatment compliance will be assessed by self-administered questionnaire.